Prior studies among non-demented participants as well as samples spanning the Alzheimer's disease-spectrum have reported higher WMH burden37-40 and greater longitudinal increases in WMH burden42,43 among APOE-ɛ4 carriers relative to carriers, with stronger associations for homozygous than heterozygous participants38 (but see Habes et al.,44 Lyall et al.,45 Lane et al. 46 and Debette et al. 47 for negative results). The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.